Studies performed in this laboratory have demonstrated that passage of Gross murine leukemia virus (GV) in adult mice results in the generation of variant viruses which differ from the parental GV with respect to the loss of antigenic epitopes associated with the virus envelope glycoprotein, SP70. These variant retroviruses appear to be generated as the result of immunoselection in the host since variant viruses have only been isolated from immunocompetent mice infected as adults and mice inoculated with virus as neonates but not from sublethally irradiated (500 R) mice which are immunosuppressed. The variations in virus epitope expression appear to be determined by the host immune response generated against specific epitopes. This anti-epitope response appears to be regulated by both H-2 and non H-2-linked genes. These genes may regulate T cell responses as well as antibody responses against particular epitopes. The goal of the studies described in this proposal is to examine the genetic regulation of the host immune response to virus epitopes which results in the generation if variant viruses and to define the molecular changes in the virus genome which result in the changes in epitope expression. The significance of these studies is related to the fact that the generation of antigenic variants may result in persistent infection and the subsequent development of leukemic in animal a resistant to parental GV. We hypothesize that the basis for this persistent infection is that, although several antigenic variants may be generated as the result of point mutation or recombination with endolenous retroviruses, only those variants which do not induce an effective immune response will replicate in the host. Isolates of the human retrovirus HlV-l (a lentivirus) which causes a persistent infection in humans resulting in the development of AlDS demonstrate variation in antigenic epitopes associated with the envelope glycoprotein. In addition isolates of HTLV-l which is associated with the development of adult T cell leukemia in humans demonstrate differences in sequences encoding the envelope glycoprotein. The murine studies described in this proposal may increase the understanding of the generation of antigenic diversity seem in these human retroviruses. Such information may be important in the a vaccine against these development.